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Even in times of a national crisis, fraudsters will go to extraordinary lengths to divert funds away from the public sector. Ogretmen, B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer 18, 33–50. https://doi.org/10.1038/nrc.2017.96 (2018). Cirillo, F. et al. The antithetic role of ceramide and sphingosine-1-phosphate in cardiac dysfunction. J. Cell Physiol. 236, 4857–4873. https://doi.org/10.1002/jcp.30235 (2021). Molecular Therapeutics Laboratory, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, AustraliaNewton, J., Lima, S., Maceyka, M. & Spiegel, S. Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy. Exp. Cell Res. 333, 195–200. https://doi.org/10.1016/j.yexcr.2015.02.025 (2015). Sphingosine kinase assays using purified recombinant SK1 (1 ng) and SK2 (10 ng) 44, 45 were performed with JTE-013 or DMSO using fatty acid-free BSA (0.1%) solubilized-sphingosine (10 µM), ATP (100 µM) and 1 μCi [γ 32P]ATP in 100 mM Tris/HCl (pH 7.4), containing 150 mM NaCl, 1 mM Na 3VO 4, 10 mM NaF (100 µl total reaction volume), incubated for 30 min at 37 °C, as described previously 46. SK1 degradation assays French, K. J. et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J. Pharmacol. Exp. Ther. 333, 129–139. https://doi.org/10.1124/jpet.109.163444 (2010).

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Fraud is a constant threat, and those who commit fraud take money away from public services and those who rely on them. The increase in fraud threat during COVID-19 reminds us that fraud is an increasingly complex and dynamic crime, and it requires skill, capability and commitment to mitigate it effectively. Human S1P lyase cDNA (SGPL1, Genbank Accession number NM_003901) was amplified from placenta cDNA and FLAG epitope-tagged at the 3′ end by PCR with oligonucleotide primers 5′-TATATAGAATTCGCCACCATGCCTAGCACAGACCTTCT-3′ and 5′-TATATAGAATTCACTTGTCATCGTCGTCCTTGTAGTCGTGGGGTTTTGGAGAACCAT-3′. The PCR product was digested with EcoRI and cloned into pcDNA3 (Invitrogen) for expression in mammalian cells. Sequencing verified the orientation and integrity of the cDNA. Quantitative RT-PCR The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism Salomone, S. & Waeber, C. Selectivity and specificity of sphingosine-1-phosphate receptor ligands: Caveats and critical thinking in characterizing receptor-mediated effects. Front. Pharmacol. 2, 9. https://doi.org/10.3389/fphar.2011.00009 (2011). Green, C. D., Maceyka, M., Cowart, L. A. & Spiegel, S. Sphingolipids in metabolic disease: The good, the bad, and the unknown. Cell Metab. 33, 1293–1306. https://doi.org/10.1016/j.cmet.2021.06.006 (2021).SK1 degradation assays were performed as described previously 47. JTE-013 treatments were compared to DMSO vehicle or SKi positive control in the presence or absence of proteasome inhibitor MG132 (10 µM). Cell survival assays This standard also includes groove recommendations for staic, hydraulic and pneumatic applications ISO3601 Size Pyne, N. J. & Pyne, S. Selectivity and specificity of sphingosine 1-phosphate receptor ligands: “off-targets” or complex pharmacology?. Front. Pharmacol. 2, 26. https://doi.org/10.3389/fphar.2011.00026 (2011).

The publication of the Counter Fraud Functional Standard reinforces the government’s commitment to fighting fraud. By meeting the requirements of this standard, public bodies are better prepared, and more able to respond to the risk of fraud against the public sector.Ikeda, H. et al. Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5. Gastroenterology 124, 459–469. https://doi.org/10.1053/gast.2003.50049 (2003).